Both a sedentary lifestyle and obesity have been demonstrated to contribute to a state of chronic, low level inflammation. Such inflammation has been implicated in the development of insulin resistance, cardiovascular disease, and type II Diabetes Mellitus, providing a link between these diseases and excess adiposity and/or physical inactivity. Thus, an increase in chronic inflammation may represent a "gateway" to the development of other inflammatory diseases. While the role of chronic inflammation in diseases of inactivity and obesity has been described, the mechanism by which pathological conditions cause an increased accumulation of chronic inflammation is not known. Based on preliminary data from our lab and others, we have speculated that the TLR4 pathway may be involved in the accumulation of chronic inflammation. Our long-term objective is to use a mechanistic approach to identify inflammatory pathways related to adiposity and inactivity. We have proposed that TLR4 signaling may be involved with the accumulation of chronic inflammation, and have previously demonstrated this by comparing active (low inflammation) to sedentary individuals (high inflammation). Blood monocytes are typically assessed as an indicator of adipose tissue macrophage activity; however, it is not known if TLR4 signaling is similar between these two cells. Also, it is not known if obesity alters monocytes and macrophages in the same manner. Other molecules (i.e. hsCRP, leptin, ghrelin, etc.) are known to be altered in the blood of obese individuals; however, it is not known if they effect TLR4 signaling. We anticipate that this study will generate a number of new and novel findings with respect to the possible relationship between TLR4 signaling, obesity, and chronic inflammation. The primary purpose of this investigation is to determine if obesity status alters TLR4 signaling and/or inflammatory cytokine production in blood monocyte and adipose tissue macrophage. [unreadable] [unreadable] [unreadable]